Levosalbutamol

Levosalbutamol
Clinical data


Trade names	Xopenex
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: A US: C (Risk not ruled out)
Routes of administration	By mouth (tablets), inhalational (MDI)
ATC code	R03AC02 (WHO) R03CC02 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	3.3–4 hours
Excretion	Urinary
Identifiers
IUPAC name 4-[(1R)-2-(tert-butylamino)-1-hydroxyethyl]- 2-(hydroxymethyl)phenol
CAS Number	34391-04-3^N
PubChem (CID)	123600
DrugBank	DB01001^N
ChemSpider	110192^Y
UNII	QF8SVZ843E^Y
KEGG	D08124^N
ChEBI	CHEBI:8746^Y
ChEMBL	CHEMBL1002^Y
ECHA InfoCard	100.113.688
Chemical and physical data
Formula	C₁₃H₂₁NO₃
Molar mass	239.311 g/mol
3D model (Jmol)	Interactive image
SMILES OCc1cc(ccc1O)[C@@H](O)CNC(C)(C)C
InChI InChI=1S/C13H21NO3/c1-13(2,3)14-7-12(17)9-4-5-11(16)10(6-9)8-15/h4-6,12,14-17H,7-8H2,1-3H3/t12-/m0/s1^Y Key:NDAUXUAQIAJITI-LBPRGKRZSA-N^Y
^NY (what is this?) (verify)

Levosalbutamol, also known as levalbuterol, is a short-acting β₂ adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence does not show that levosalbutamol works better than salbutamol, thus there may not be sufficient justification for prescribing it.^[1]

The drug is the (R)-(−)-enantiomer of its prototype drug salbutamol. It is available in some countries in generic formulations from pharmaceutical companies including Cipla, Teva, and Dey, among others.

Medical use

Levosalbutamol's bronchodilator properties give it indications in treatment of COPD (chronic obstructive pulmonary disease, also known as chronic obstructive lung disease) and asthma. Like other bronchodilators, it acts by relaxing smooth muscle in the bronchial tubes, and thus shortening or reversing an acute "attack" of shortness of breath or difficulty breathing. Unlike some slower-acting bronchodilators, it is not indicated as a preventative of chronic bronchial constriction.

Comparison to salbutamol

A 2013 systematic review of the drug's use as a treatment for acute asthma found that it "was not superior to albuterol regarding efficacy and safety in subjects with acute asthma." The review concluded: "We suggest that levalbuterol should not be used over albuterol for acute asthma."^[1] Levalbuterol is notably more costly.^[2]^[3]

Adverse effects

Generally, levosalbutamol is well tolerated. Common mild side-effects include an elevated heart rate, muscle cramps, and gastric upset (including heartburn and diarrhea).^[4]

Symptoms of overdose in particular include: collapse into a seizure; chest pain (possible precursor of a heart attack); fast, pounding heartbeat, which may cause raised blood pressure (hypertension); irregular heartbeat (cardiac arrhythmia), which may cause paradoxical lowered blood pressure (hypotension); nervousness and tremor; headache; dizziness and nausea/vomiting; weakness or exhaustion (medical fatigue); dry mouth; and insomnia.^[4]

Rarer side effects may indicate a dangerous allergic reaction. These include: paradoxical bronchospasm (shortness of breath and difficulty breathing); skin itching, rash, or hives (urticaria); swelling (angioedema) of any part of the face or throat (which can lead to voice hoarseness), or swelling of the extremities.^[4]

Pharmacology

Levosalbutamol has similar pharmacokinetic and pharmacodynamic properties to salbutamol.^[5]

Mechanism of action

Activation of β₂ adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.

Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional agonist that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges.

While it is recognized that β₂ adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta receptors in the human heart, 10–50% of which are β₂ adrenergic receptors. The precise function of these receptors has not been established. However, all β adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, and restlessness symptoms, and/or electrocardiographic (ECG) changes.

Approval and names

Levosalbutamol is the INN while levalbuterol is the USAN.

Levalbuterol was originally available only as a solution for nebulizer and eventually become available as a CFC-free metered-dose inhaler under the trade name Xopenex HFA (levalbuterol tartrate inhalation aerosol). The FDA approval date was on March 11, 2005.^[6]

It is also available in India as a combination drug Duolin (levosalbutamol/ipratropium bromide).^[7]

References

1 2 Jat, K. R.; Khairwa, A. (April 2013). "Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis". Pulmonary Pharmacology & Therapeutics. 26 (2): 239–248. doi:10.1016/j.pupt.2012.11.003. PMID 23207739.
↑ Schreck DM, Babin S (November 2005). "Comparison of racemic albuterol and levalbuterol in the treatment of acute asthma in the ED". Am J Emerg Med. 23 (7): 842–7. doi:10.1016/j.ajem.2005.04.003. PMID 16291438.
↑ Hendeles L, Hartzema A (September 2003). "Levalbuterol is not more cost-effective than albuterol for COPD". Chest. 124 (3): 1176; author reply 1176–8. doi:10.1378/chest.124.3.1176. PMID 12970057.
1 2 3 American Society of Health-System Pharmacists (1 September 2010). "Levalbuterol Oral Inhalation". MedlinePlus. Bethesda, Maryland: U.S. National Library of Medicine, National Institutes of Health. Retrieved 7 January 2015.
↑ Xenopex [package insert] Marlborough, MA: Sunovion Pharmaceuticals. 2014
↑ (See Official FAQ)
↑

Adrenergic receptor modulators

α₁

Agonists 6-FNE Amidephrine Anisodine Buspirone Cirazoline Corbadrine Dexisometheptene Dipivefrine Dopamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etilefrine Etilevodopa Ethylnorepinephrine Indanidine Isometheptene L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Melevodopa Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine (drug) Oxymetazoline Phenylephrine Phenylpropanolamine Pseudoephedrine Synephrine Tetryzoline Tiamenidine XP21279 Xylometazoline

Antagonists Abanoquil Adimolol Ajmalicine Alfuzosin Amosulalol Anisodamine Arotinolol Atiprosin Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone) Benoxathian Buflomedil Bunazosin Carvedilol Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., ergotamine, dihydroergotamine, lisuride, terguride) Etoperidone Eugenodilol Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 Labetalol mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Nefazodone Neldazosin Niaprazine Nicergoline Niguldipine Pardoprunox Pelanserin Phendioxan Phenoxybenzamine Phentolamine Piperoxan Prazosin Quinazosin Ritanserin Silodosin Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Trazodone Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine) Trimazosin Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Urapidil WB-4101 Zolertine

α₂

Agonists (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Cannabivarin Clonidine Corbadrine Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Droxidopa (L-DOPS) Etilevodopa Ephedrine Ergotamine Epinephrine Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Lofexidine Medetomidine Melevodopa Methyldopa Mivazerol Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan Pseudoephedrine Rilmenidine Romifidine Talipexole Tetrahydrozoline Tiamenidine Tizanidine Tolonidine Urapidil XP21279 Xylazine Xylometazoline

Antagonists 1-PP Adimolol Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine, clozapine, lurasidone, paliperidone, quetiapine, risperidone, zotepine) Azapirones (e.g., buspirone, tandospirone) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan mCPP Mianserin Mirtazapine NAN-190 Olanzapine Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine SB-269970 Setiptiline Spiroxatrine Sunepitron Tolazoline Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Yohimbine

Agonists Abediterol Alifedrine Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Carmoterol Cimaterol Clenbuterol Corbadrine Denopamine Dipivefrine Dobutamine Dopamine Dopexamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etafedrine Etilefrine Etilevodopa Ethylnorepinephrine Fenoterol Formoterol Hexoprenaline Higenamine Indacaterol Isoetarine Isoprenaline Isoxsuprine L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Levosalbutamol Mabuterol Melevodopa Methoxyphenamine Methyldopa Mirabegron Norepinephrine Orciprenaline Oxyfedrine PF-610355 Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Pseudoephedrine Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Vilanterol Xamoterol XP21279 Zilpaterol Zinterol

Antagonists Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Bufuralol Bunitrolol Bunolol Bupranolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levomoprolol Medroxalol Mepindolol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nebivolol Nifenalol Nipradilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Penbutolol Pindolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol Talinolol Tazolol Tertatolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Xibenolol Xipranolol

See also: Dopaminergics

Melatonergics

Serotonergics

Monoamine reuptake and release modulators

Monoamine metabolism modulators

Monoamine neurotoxins

Drugs for obstructive airway diseases: asthma/COPD (R03)

Adrenergics, inhalants

Short-acting β₂ agonists	Bitolterol Carbuterol Fenoterol Isoetarine Pirbuterol Procaterol Reproterol Rimiterol Salbutamol (albuterol)^#/Levosalbutamol (levalbuterol) Terbutaline Tulobuterol

Long-acting β₂ agonists	Bambuterol Clenbuterol Formoterol/Arformoterol Salmeterol Salmefamol

Ultra-long-acting β₂ agonists	Abediterol Carmoterol Indacaterol Olodaterol Vilanterol

Other	Epinephrine^# Hexoprenaline Isoprenaline (isoproterenol) Orciprenaline (metaproterenol)

Glucocorticoids

Anticholinergics/
muscarinic antagonist

Mast cell stabilizers

Xanthines

Eicosanoid inhibition

Leukotriene antagonists	Montelukast Pranlukast Zafirlukast

Arachidonate 5-lipoxygenase inhibitors	Zileuton

Thromboxane receptor antagonists	Ramatroban Seratrodast

Non-xanthine PDE4 inhibitors	Ibudilast Roflumilast

Others/unknown

Combination products

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Phenethylamines

Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-B-FLY βk-2C-B 2C-C 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-I 2C-N 2C-P 2C-SE 2C-T 2C-T-2 2C-T-4 2C-T-7 2C-T-8 2C-T-9 2C-T-13 2C-T-15 2C-T-16 2C-T-17 2C-T-21 2C-TFM 2C-YN Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA

Amphetamines	Psychedelics: 3C-BZ 3C-E 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamine Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L -Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA Phenpromethamine PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA MDEA MDHMA MDMA MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DFMDA Selegiline (also D -Deprenyl)

Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine

Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone

Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine

Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone

Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D -DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L -DOPA (Levodopa) L -DOPS (Droxidopa) L -Phenylalanine L -Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine

Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Theodrenaline Thiamphenicol UWA-101

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